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Editorial
. 2022 Jun 20:11:e80232.
doi: 10.7554/eLife.80232.

Gatekeeping astrocyte identity

Alexis Cooper  1   2 , Benedikt Berninger  1   2   3
Affiliations
Editorial

Gatekeeping astrocyte identity

Alexis Cooper et al. Elife. .

Abstract

New findings cast doubt on whether suppressing the RNA-binding protein PTBP1 can force astrocytes to become dopaminergic neurons.

Keywords: PTBP1; astrocyte; astrocyte-to-neuron conversion; brain repair; lineage reprogramming; mouse; neuroscience; parkinson's disease; regenerative medicine; stem cells.

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Conflict of interest statement

AC, BB No competing interests declared

Figures

Figure 1.
Figure 1.. Deactivating PTBP1 in astrocytes fails to convert the cells into neurons.
(A) The hypothesis tested by Chen et al. is that the protein PTBP1 stops astrocytes (pale pink) from becoming neurons (grey). (B) Adeno-associated viruses (green) can deliver the genetic information necessary to deactivate PTBP1 in astrocytes which have been genetically tagged (red). This potentially allows the cells to be converted into dopaminergic neurons which still carry the tag (red) reflecting that they have originated from astrocytes, as well as the viral label (green). (C) Chen et al. used a mouse model in which astrocyte origin could be traced to investigate whether knocking down PTBP1 using adeno-associated viruses may lead to the cells becoming dopaminergic neurons (DA carrying the red tag); this turned out not to be the case (red cross). Instead, dopaminergic neurons carrying the viral signal (green-only cells) were identified, which did not originate from astrocytes. (D) Similar experiments were conducted in a mouse model of Parkinson’s disease. In this instance, a toxin was introduced to kill endogenous dopaminergic neurons and render resting astrocytes reactive; in this injury-triggered state, astrocytes exhibit features associated with stem cells. Deactivating PTBP1 in reactive astrocytes again failed to turn them into neurons, and the mice still exhibited motor deficits.
See this image and copyright information in PMC

Comment on

  • doi: 10.7554/eLife.75636

References

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